The injection of a mixture of autologous lymphokines into some of the metastatic nodules of patients with multiple nodules of malignant melanoma leads to the development of a mononuclear cell infiltrate in nodules that have never been injected as well as those that were injected. In one half of 38 patients, this infiltrate was associated with a complete and permanent regression of most or all metastatic nodules, both noninjected and injected. These observations indicate that metastatic melanoma cells can bear antigens capable of serving as targets for host cytotoxic lymphocytes, even though the melanoma cells by themselves normally do not provoke the formation of cytotoxic lymphocytes. These findings also indicate that the injection of lymphokines into metastatic melanoma nodules leads to the formation of cytotoxic lymphocytes that are active in noninjected nodules. We are determining the phenotype and function of the lymphocytes present in these infiltrates associated with regressing nodules. We also will investigate the roles of lymphokines and different subpopulations of lymphocytes in the generation of lymphocytes cytotoxic to autologous melanoma cells in vitro in order to establish a model for the phenomenon observed in vivo. These studies will provide clues as to which soluble factors are involved in the lymphokine-initiated regressions of melanoma in vivo. (HF)